title: 18F-FDG PET/CT for early prediction of response to neoadjuvant lapatinib, trastuzumab, and their combination in HER2-positive breast cancer: results from Neo-ALTTO.
abstract: Molecular imaging receives increased attention for selecting patients who will benefit from targeted anticancer therapies. Neo-ALTTO (Neoadjuvant Lapatinib and/or Trastuzumab Treatment Optimisation) enrolled 455 women with invasive human epidermal growth factor receptor 2 (HER2)-positive breast cancer and compared rates of pathologic complete response (pCR) to neoadjuvant lapatinib, trastuzumab, and their combination. Each anti-HER2 therapy was given alone for 6 wk, followed by 12 wk of the same therapy plus weekly paclitaxel. The early metabolic effects of the anti-HER2 therapies on the primary tumors and their predictive values for pCR were assessed in a subset of patients.
  
  
  METHODS
  Eighty-six patients underwent (18)F-FDG PET/CT at baseline and weeks 2 and 6 of anti-HER2 treatment. An imaging core laboratory provided central validation, and 2 independent reviewers, masked to assigned treatment arm and clinical outcomes, performed consensus (18)F-FDG PET/CT readings. Maximum standardized uptake value (SUVmax) reductions from baseline were used to measure metabolic response.
  
  
  RESULTS
  Seventy-seven of the 86 enrolled patients presented an evaluable baseline (18)F-FDG PET/CT scan; of these, 68 and 66 were evaluable at weeks 2 and 6, respectively. Metabolic responses in the primary tumors were evident after 2 wk of targeted therapy and correlated highly with metabolic responses at week 6 (R(2) = 0.81). pCRs were associated with greater SUVmax reductions at both time points. Mean SUVmax reductions for pCR and non-pCR, respectively, were 54.3% versus 32.8% at week 2 (P = 0.02) and 61.5% versus 34.1% at week 6 (P = 0.02). (18)F-FDG PET/CT metabolic response rates at weeks 2 and 6 were 71.6% and 60%, respectively using European Organization for Research and Treatment of Cancer criteria; pCR rates were twice as high for (18)F-FDG PET/CT responders than nonresponders (week 2: 42% vs. 21%, P = 0.12; week 6: 44% vs. 19%, P = 0.05).
  
  
  CONCLUSIONS
  Early metabolic assessment using (18)F-FDG PET/CT can identify patients with an increased likelihood of pCR after neoadjuvant trastuzumab, lapatinib, or their combination when given with chemotherapy.
authors.affiliation: Nuclear Medicine Department, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Geraldine
authors.initials: G
authors.lastname: Gebhart
authors.forename: Cristina
authors.initials: C
authors.lastname: Gámez
authors.forename: Eileen
authors.initials: E
authors.lastname: Holmes
authors.forename: Javier
authors.initials: J
authors.lastname: Robles
authors.forename: Camilo
authors.initials: C
authors.lastname: Garcia
authors.forename: Montserrat
authors.initials: M
authors.lastname: Cortés
authors.forename: Evandro
authors.initials: E
authors.lastname: de Azambuja
authors.forename: Karine
authors.initials: K
authors.lastname: Fauria
authors.forename: Veerle
authors.initials: V
authors.lastname: Van Dooren
authors.forename: Gursel
authors.initials: G
authors.lastname: Aktan
authors.forename: Maria Antonia
authors.initials: MA
authors.lastname: Coccia-Portugal
authors.forename: Sung-Bae
authors.initials: SB
authors.lastname: Kim
authors.forename: Peter
authors.initials: P
authors.lastname: Vuylsteke
authors.forename: Hervé
authors.initials: H
authors.lastname: Cure
authors.forename: Holger
authors.initials: H
authors.lastname: Eidtmann
authors.forename: José
authors.initials: J
authors.lastname: Baselga
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart
authors.forename: Patrick
authors.initials: P
authors.lastname: Flamen
authors.forename: Serena
authors.initials: S
authors.lastname: Di Cosimo
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D000077341:Lapatinib; D020360:Neoadjuvant Therapy; D049268:Positron-Emission Tomography; D011799:Quinazolines / Q000008:administration & dosage / Q000627:therapeutic use; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D019788:Fluorodeoxyglucose F18; D000077341:Lapatinib; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: 18F-FDG-PET/CT; anti-HER2 drugs; early response assessment